Osteoarthritis (OA) is among the most prevalent chronic afflictions of the population over 65, and the most frequent arthritic complaint. During the course of the current TNH grant, we completed a clinical assessment of the prevalence of OA in the old-old population (mean age 86) of a nursing home, and conducted a follow-up two years later. These subjects were at one end of the spectrum of OA; now we wish to learn more about the earlier phases of the disease and examine its natural history by assessing factors in the joint that may be associated with stabilization or progression of OA. Our approach is to identify 400 subjects over a wide age range (20-85) in the first two years of the study who present with knee complaints and a joint effusion, and to conduct a follow-up in the next two years. The clinical condition with respect to the knee will be identified, and in addition, demographic, medical history, functional, mental status and psychological assessments will be done to link these patients with the "core" of the TNH. With informed consent of the three indicated approaches to the knee will be taken by the orthopedic surgeons: aspiration of the joint fluid only, arthroscopy, or total knee replacement (TKR). In every instance, synovial fluid will be obtained and we will carry out two major lines of biological research on the joint fluid: (1) measurements of markers of chronic inflammation, including some of the secretory products of macrophages and platelets that may contribute to cartilage breakdown; (2) assays for heparin-binding growth factors already identified by us in preliminary studies as platelet-derived growth factor, anionic, and cationic fibroblast growth factors. It it our belief that these growth factors may stimulate attempts at articular repair and remodelling. Since these growth factors have not previously been identified in joint fluid, our findings are of great inherent interest in terms of their cell(s) of origin and biological functions within the osteoarthritic joint. Where arthroscopy of TKR is carried out, cartilage and synovial membrane samples will also be obtained for histological studies. We will seek to determine whether the parameters associated with clinical joint examination and radiographic findings may be corelated with the quantitative levels of the biological markers in the fluid to permit predictions to be made about stability or progression of OA.